The proposed work deals with the anatomical neurochemical identification of the substrate of cocaine abuse. Studies of intravenous stimulant self-administration, intracranial self-stimulation, and drug-self stimulation interactions are planned in the rat; these phenomena will be studied under conditions of pharmacological treatment, lesions, and selective brain placements of electrodes and injection cannulae in an attempt to delineate the pathways activated by stimulation reward and drug reward and to determine the degree to which a variety of rewards share activation of such pathways in common. Of first interest are the brain dopamine pathways implicated in both brain stimulation and cocaine reward by dopamine blockade studies; dopamine pathways will be mapped at their terminal fields for self-stimulation in relation to dopamine fluorescence. Septum, accumbens, striatum and frontal and entorhinal cortex are of particular interest. Self-administration of heroin, barbiturates and ethanol will be explored and challenged with dopamine blockers, opiate antagonists and GABA agonists and antagonists; self-administration of these agents and cocaine will also be challenged with lesions, but under other funding. The effects of cocaine, amphetamine, heroin, barbiturate, ethanol and benzodiazepines will be assessed on intracranial self-examination. Major parametric work will be done in this area, exploring the drugs in order of listing. Dose response time course studies will be done with threshold and rate-intensity measures. Major attention will be paid to repeated small intravenous doses which correspond to slightly more, the same, or slightly less than the hourly drug intakes that the animals self-administer in other tests. Reward facilitation by these drugs of abuse will be challenged by naloxone and locus coeruleus lesions. Intracerebroventricular or intracranial injections of the drugs of abuse will be explored in this paradigm if and when they are established as viable routes for self-administration in work funded elsewhere; this will be done to localize the site of rewarding action of the drugs and to localize the site of reward facilitation. The working hypothesis that drugs facilitate self-stimulation at the site of their own rewarding effects will be carefully examined at all stages of this work.